NOTCH1 mutation (PEST domain)

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`BIO-NOTCH1-MUTATION`
Type	Biomarker
Aliases	NOTCH1 mutationМутація NOTCH1 (PEST domain)
Status	reviewed 2026-04-25 \| pending_clinical_signoff
Diseases	None declared
Sources	`SRC-NCCN-BCELL-2025`

Biomarker Facts

Biomarker type	gene_mutation
Mutation details	{"functional_impact": "stabilization of activated NOTCH1 → constitutive NF-κB + MYC signaling", "gene": "NOTCH1", "variant_type": "frameshift / nonsense in PEST domain (most commonly p.P2514Rfs*4)"}
Measurement	MethodNGS panel covering PEST domain hot-spots Unitscategorical (positive \| negative)
Related biomarkers	None declared

Notes

Cross-disease relevance: - **CLL/SLL** (~10-15%): adverse prognostic marker — shorter OS, higher transformation rate to Richter (DLBCL). Often co-occurs with trisomy 12 + IGHV-unmutated. Modest impact on 1L choice in BTKi era but flag for early Richter watch. - **MCL** (~5-10%): adverse subset; may favor BTKi over chemoimmuno. - **T-ALL** (~50%): defining, drives γ-secretase inhibitor research. Currently informational in CLL/MCL; not direct algorithm driver. Future: 2L+ stratification + earlier Richter surveillance.

Used By

Actionability

BMA-NOTCH1-ACTIVATING-CLL - NOTCH1 activating mutations (~10-15% of CLL) — adverse prognostic; reduced response to an...
BMA-NOTCH1-ACTIVATING-DLBCL-NOS - NOTCH1 mutations in DLBCL — uncommon; not therapy-selecting.
BMA-NOTCH1-ACTIVATING-MCL - NOTCH1 mutations in ~10-15% of MCL — adverse prognostic; not directly targeted. BTKi-base...
BMA-NOTCH1-ACTIVATING-T-ALL - NOTCH1 activating mutations occur in >50% of T-ALL (HD and PEST domains). Gamma-secretase...

Biomarker

BIO-CLL-HIGH-RISK-GENETICS - CLL high-risk genetics (TP53 / del(17p) / IGHV-unmutated / complex karyotype)

Diseases

DIS-SALIVARY - Salivary gland carcinoma

Indications

IND-CLL-1L-BTKI - IND-CLL-1L-BTKI
IND-CLL-1L-VENO - IND-CLL-1L-VENO
IND-CLL-1L-ZANUBRUTINIB - IND-CLL-1L-ZANUBRUTINIB

Red flag

RF-SALIVARY-HIGH-RISK-BIOLOGY - Salivary gland carcinoma with actionable molecular driver: ETV6-NTRK3 fusion (mammary ana...